Lymphotoxin beta receptor signaling limits mucosal damage through driving IL-23 production by epithelial cells.

ABSTRACT: The immune mechanisms regulating epithelial cell repair after injury remain poorly defined. We demonstrate here that lymphotoxin beta receptor (LT?R) signaling in intestinal epithelial cells promotes self-repair after mucosal damage. Using a conditional gene-targeted approach, we demonstrate that LT?R signaling in intestinal epithelial cells is essential for epithelial interleukin-23 (IL-23) production and protection against epithelial injury. We further show that epithelial-derived IL-23 promotes mucosal wound healing by inducing the IL-22-mediated proliferation and survival of epithelial cells and mucus production. Additionally, we identified CD4(-)CCR6(+)T-bet(-) RAR-related orphan receptor gamma t (ROR?t)(+) lymphoid tissue inducer cells as the main producers of protective IL-22 after epithelial damage. Thus, our results reveal a novel role for LT?R signaling in epithelial cells in the regulation of intestinal epithelial cell homeostasis to limit mucosal damage.

SUBMITTER: Macho-Fernandez E 

PROVIDER: S-EPMC4364000 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature